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SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer †

The Polyribonucleotide nucleotidyltransferase 1 gene (PNPT1) encodes polynucleotide phosphorylase (PNPase), a 3′-5′ exoribonuclease involved in mitochondrial RNA degradation and surveillance and RNA import into the mitochondrion. Here, we have characterized the PNPT1 promoter by in silico analysis,...

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Detalles Bibliográficos
Autores principales: Ventura, Ignacio, Revert, Fernando, Revert-Ros, Francisco, Gómez-Tatay, Lucía, Prieto-Ruiz, Jesús A., Hernández-Andreu, José Miguel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570217/
https://www.ncbi.nlm.nih.gov/pubmed/36232701
http://dx.doi.org/10.3390/ijms231911399
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author Ventura, Ignacio
Revert, Fernando
Revert-Ros, Francisco
Gómez-Tatay, Lucía
Prieto-Ruiz, Jesús A.
Hernández-Andreu, José Miguel
author_facet Ventura, Ignacio
Revert, Fernando
Revert-Ros, Francisco
Gómez-Tatay, Lucía
Prieto-Ruiz, Jesús A.
Hernández-Andreu, José Miguel
author_sort Ventura, Ignacio
collection PubMed
description The Polyribonucleotide nucleotidyltransferase 1 gene (PNPT1) encodes polynucleotide phosphorylase (PNPase), a 3′-5′ exoribonuclease involved in mitochondrial RNA degradation and surveillance and RNA import into the mitochondrion. Here, we have characterized the PNPT1 promoter by in silico analysis, luciferase reporter assays, electrophoretic mobility shift assays (EMSA), chromatin immunoprecipitation (ChIP), siRNA-based mRNA silencing and RT-qPCR. We show that the Specificity protein 1 (SP1) transcription factor and Nuclear transcription factor Y (NFY) bind the PNPT1 promoter, and have a relevant role regulating the promoter activity, PNPT1 expression, and mitochondrial activity. We also found in Kaplan–Meier survival curves that a high expression of either PNPase, SP1 or NFY subunit A (NFYA) is associated with a poor prognosis in liver cancer. In summary, our results show the relevance of SP1 and NFY in PNPT1 expression, and point to SP1/NFY and PNPase as possible targets in anti-cancer therapy.
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spelling pubmed-95702172022-10-17 SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer † Ventura, Ignacio Revert, Fernando Revert-Ros, Francisco Gómez-Tatay, Lucía Prieto-Ruiz, Jesús A. Hernández-Andreu, José Miguel Int J Mol Sci Article The Polyribonucleotide nucleotidyltransferase 1 gene (PNPT1) encodes polynucleotide phosphorylase (PNPase), a 3′-5′ exoribonuclease involved in mitochondrial RNA degradation and surveillance and RNA import into the mitochondrion. Here, we have characterized the PNPT1 promoter by in silico analysis, luciferase reporter assays, electrophoretic mobility shift assays (EMSA), chromatin immunoprecipitation (ChIP), siRNA-based mRNA silencing and RT-qPCR. We show that the Specificity protein 1 (SP1) transcription factor and Nuclear transcription factor Y (NFY) bind the PNPT1 promoter, and have a relevant role regulating the promoter activity, PNPT1 expression, and mitochondrial activity. We also found in Kaplan–Meier survival curves that a high expression of either PNPase, SP1 or NFY subunit A (NFYA) is associated with a poor prognosis in liver cancer. In summary, our results show the relevance of SP1 and NFY in PNPT1 expression, and point to SP1/NFY and PNPase as possible targets in anti-cancer therapy. MDPI 2022-09-27 /pmc/articles/PMC9570217/ /pubmed/36232701 http://dx.doi.org/10.3390/ijms231911399 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ventura, Ignacio
Revert, Fernando
Revert-Ros, Francisco
Gómez-Tatay, Lucía
Prieto-Ruiz, Jesús A.
Hernández-Andreu, José Miguel
SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer †
title SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer †
title_full SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer †
title_fullStr SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer †
title_full_unstemmed SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer †
title_short SP1 and NFY Regulate the Expression of PNPT1, a Gene Encoding a Mitochondrial Protein Involved in Cancer †
title_sort sp1 and nfy regulate the expression of pnpt1, a gene encoding a mitochondrial protein involved in cancer †
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570217/
https://www.ncbi.nlm.nih.gov/pubmed/36232701
http://dx.doi.org/10.3390/ijms231911399
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